Evolution of Intestinal Microbiota in Patients With Juvenile Spondylarthropathy According to Typology of Treatment (MESAJ)

Descriptive Study on the Evolution of Intestinal Microbiota Profiles in Patients With Juvenile Spondylarthropathy According to the Typology of Treatment and Response to it: A Descriptive, Prospective Pilot Study

Idiopathic juvenile arthritis includes 20% of patients with arthritis with enthesitis or juvenile spondyloarthropathy. This is treated with anti-inflammatory drugs and then followed by biotherapy with DMARDs (Drugs Modifying the Activity of Rheumatic Disease) if the former are insufficient. Methotrexate (MTX) may also be used before these biotherapies. Recently, in adults, a particular profile of intestinal microbiota has been shown to alter the availability of MTX making it in efficient. Knowing that pediatric patients with juvenile spondyloarthropathy have an imbalance of their intestinal flora (dysbiosis) the investigators wanted to explore whether DMARDs could have a similar impact on the microbiota of these young patients and alter the response to treatment.

Study Overview

• Status: Recruiting
• Conditions: Spondylarthropathies
• Intervention / Treatment: Other: Stool collection at the patient's home.; Diagnostic test: Blood test

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tu-Anh TRAN, Professor; Phone Number: +33 4 66 32 86; Email: tu.anh.tran@chu-nimes.fr
• Study Contact Backup: Name: Jean-Philippe LAVIGNE, Professor; Phone Number: +334 66 68 32 02; Email: jean.philippe.lavigne@chu-nimes.fr

Study Locations

• France
  • Marseille, France
    • Recruiting
    • APHM, Hôpital Nord
    • Contact: Diego URBINA
  • Gard
    • Nîmes, Gard, France, 30029
      • Recruiting
      • Nîmes University Hospital
      • Principal Investigator: Tu-Anh TRAN, Prof.
      • Sub-Investigator: Anne FILLERON, Dr.
      • Sub-Investigator: Renaud CEZAR, Hospital engineer
      • Sub-Investigator: Catherine DUNYACH-REMY, Dr.
      • Sub-Investigator: Jean-Philippe LAVIGNE, Prof.
      • Contact: Anissa MEGZARI; Phone Number: +33 4 66 68 42 36; Email: drc@chu-nimes.fr
  • Hérault
    • Montpellier, Hérault, France, 34295
      • Recruiting
      • Montpellier University Hospital, Arnaud de Villeneuve Hospital
      • Contact: Eric JEZIORSKI, Dr.; Phone Number: +33 4 67 33 22 86; Email: e-jeziorski@chu-montpellier.fr
      • Principal Investigator: Eric JEZIORSKI, Dr.
      • Sub-Investigator: Aurelia CARBASSE, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 16 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients aged over 8 and under 17 years old (included).
• Patients diagnosed with arthritis with juvenile enthesitis according to the International League of Associations for Rheumatology (ILAR) criteria.
• Patients who haven't been treated by Methotrexate or biotherapy for at least 3 months.
• Patients who haven't been treated by cortisone for over a month.
• Patients whose parents have given written informed consent.
• Patients for whom the consent form has been signed by their legal guardian.
• Patients covered by the Social Security System or benefitting from private health insurance.

Exclusion Criteria:

• Patients enrolled in another category 1 study or who have already taken part in a category 1 study within 3 months prior to inclusion.
• Patients who are within an exclusion period determined by another study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Profile AB; Patients on non-steroidal anti-inflammatory drugs followed by biotherapy.	Other: Stool collection at the patient's home.; Stool samples will be taken from each patient to look for changes in intestinal microbiota. These collections will be made on Day 0 +24h, 24 hours before the 1st follow-up visit after 1 month of treatment with non-steroidal anti-inflammatory drugs, 24 hours after the second follow-up visit (between months 3 and 4) and finally, at the end of treatment.; Diagnostic test: Blood test; 7 ml of blood will be taken from each patient before treatment i.e. at the inclusion visit and at the end of treatment.
Experimental: Profile AM; Patients on non-steroidal anti-inflammatory drugs followed by treatment with methotrexate.	Other: Stool collection at the patient's home.; Stool samples will be taken from each patient to look for changes in intestinal microbiota. These collections will be made on Day 0 +24h, 24 hours before the 1st follow-up visit after 1 month of treatment with non-steroidal anti-inflammatory drugs, 24 hours after the second follow-up visit (between months 3 and 4) and finally, at the end of treatment.; Diagnostic test: Blood test; 7 ml of blood will be taken from each patient before treatment i.e. at the inclusion visit and at the end of treatment.
Experimental: Profile AMB; Patients on non-steroidal anti-inflammatory drugs followed by treatment with methotrexate and then biotherapy if there is no improvement with methotrexate.	Other: Stool collection at the patient's home.; Stool samples will be taken from each patient to look for changes in intestinal microbiota. These collections will be made on Day 0 +24h, 24 hours before the 1st follow-up visit after 1 month of treatment with non-steroidal anti-inflammatory drugs, 24 hours after the second follow-up visit (between months 3 and 4) and finally, at the end of treatment.; Diagnostic test: Blood test; 7 ml of blood will be taken from each patient before treatment i.e. at the inclusion visit and at the end of treatment.
Experimental: Profile A; Patients on non-steroidal anti-inflammatory drugs.	Other: Stool collection at the patient's home.; Stool samples will be taken from each patient to look for changes in intestinal microbiota. These collections will be made on Day 0 +24h, 24 hours before the 1st follow-up visit after 1 month of treatment with non-steroidal anti-inflammatory drugs, 24 hours after the second follow-up visit (between months 3 and 4) and finally, at the end of treatment.; Diagnostic test: Blood test; 7 ml of blood will be taken from each patient before treatment i.e. at the inclusion visit and at the end of treatment.
Experimental: Profile M; methotrexate alone	Other: Stool collection at the patient's home.; Stool samples will be taken from each patient to look for changes in intestinal microbiota. These collections will be made on Day 0 +24h, 24 hours before the 1st follow-up visit after 1 month of treatment with non-steroidal anti-inflammatory drugs, 24 hours after the second follow-up visit (between months 3 and 4) and finally, at the end of treatment.; Diagnostic test: Blood test; 7 ml of blood will be taken from each patient before treatment i.e. at the inclusion visit and at the end of treatment.
Experimental: Profile B; biotherapy alone	Other: Stool collection at the patient's home.; Stool samples will be taken from each patient to look for changes in intestinal microbiota. These collections will be made on Day 0 +24h, 24 hours before the 1st follow-up visit after 1 month of treatment with non-steroidal anti-inflammatory drugs, 24 hours after the second follow-up visit (between months 3 and 4) and finally, at the end of treatment.; Diagnostic test: Blood test; 7 ml of blood will be taken from each patient before treatment i.e. at the inclusion visit and at the end of treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs alone (Profile A). Number of species detected in the intestinal microbiota.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department.The number of species detected in the intestinal microbiota will be recorded.	24 hours after inclusion
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs alone (Profile A). Distribution of species detected in the intestinal microbiota.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department.The distribution of the various bacterial species detected in the intestinal microbiota will be recorded.	24 hours after inclusion
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs alone (Profile A). Diversity of species detected in the intestinal microbiota.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department. The diversity index according to the number of species and the number of functional groups will be recorded.	24 hours after inclusion
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs alone (Profile A). Number of species detected in the intestinal microbiota.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department.The number of species detected in the intestinal microbiota will be recorded. - the diversity index according to the number of species and the number of functional groups.	After 1 month of treatment
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs alone (Profile A). Distribution of species detected in the intestinal microbiota.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department.The distribution of the various bacterial species detected in the intestinal microbiota will be recorded.	After 1 month of treatment
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs alone (Profile A). Diversity of species detected in the intestinal microbiota.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department.The diversity index according to the number of species and the number of functional groups will be recorded.	After 1 month of treatment
Response to treatment in patients treated with non-steroidal anti-inflammatory drugs alone (Profile A)	The JADAS CRP clinical score will be used to rate the degree of activity of the disease. The Juvenile Arthritis Disease Activity Score (JADAS) is a recently developed composite tool for scoring disease activity in juvenile idiopathic arthritis. It is a composite disease activity score including four measures: the physician's global assessment of disease activity;; the parent/guardian's or patient's global assessment of overall wellbeing;; number of joints with active arthritis; and; C-reactive protein (CRP) which has been determined as an alternative inflammatory marker to the Erythrocyte Sedimentation Rate ESR. JADAS-CRP was calculated similarly to the original JADAS as the simple sum of its four components, yielding a global score of 0-40, 0-57 and 0-101 depending on the joint count used for the JADAS10-CRP, JADAS27-CRP and JADAS71-CRP, respectively.	After 1 month of treatment
Response to treatment in patients treated with non-steroidal anti-inflammatory drugs alone (Profile A). Number of flare-ups.	The number of flare-ups in patients treated with non-steroidal anti-inflammatory drugs alone (Profile A) will be noted.	After 1 month of treatment
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate (Profile AM). Number of species detected in the intestinal microbiota.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department.The number of species detected in the intestinal microbiota will be recorded.	24 hours after inclusion
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate (Profile AM). Distribution of species detected in the intestinal microbiota.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department.The distribution of the various bacterial species detected in the intestinal microbiota will be recorded.	24 hours after inclusion
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate (Profile AM). Diversity of species detected in the intestinal microbiota.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department.The diversity index according to the number of species and the number of functional groups will be recorded.	24 hours after inclusion
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate (Profile AM).Number of species.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department. The number of species detected in the intestinal microbiota will be recorded.	After 1 month of treatment
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate (Profile AM). Distribution of species.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department. The distribution of the various bacterial species detected in the intestinal microbiota will be recorded.	After 1 month of treatment
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate (Profile AM). Diversity of species.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department. The diversity index according to the number of species and the number of functional groups will be recorded.	After 1 month of treatment
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate (Profile AM). Number of species.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department. The number of species detected in the intestinal microbiota will be recorded.	After 6 months of treatment
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate (Profile AM). Distribution of species.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department. The distribution of the various bacterial species in the microbiota will be recorded.	After 6 months of treatment
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate (Profile AM). Diversity of species.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department. The diversity index according to the number of species and the number of functional groups will be recorded.	After 6 months of treatment
Response to treatment in patients treated with non-steroidal anti-inflammatory drugs for 1 month followed by methotrexate for 5 months (Profile AM)	The JADAS CRP clinical score will be used to rate the degree of activity of the disease. The Juvenile Arthritis Disease Activity Score (JADAS) is a recently developed composite tool for scoring disease activity in juvenile idiopathic arthritis. It is a composite disease activity score including four measures: the physician's global assessment of disease activity;; the parent/guardian's or patient's global assessment of overall wellbeing;; number of joints with active arthritis; and; C-reactive protein (CRP) which has been determined as an alternative inflammatory marker to the Erythrocyte Sedimentation Rate ESR. JADAS-CRP was calculated similarly to the original JADAS as the simple sum of its four components, yielding a global score of 0-40, 0-57 and 0-101 depending on the joint count used for the JADAS10-CRP, JADAS27-CRP and JADAS71-CRP, respectively.	After 6 months of treatment
Response to treatment in patients treated with non-steroidal anti-inflammatory drugs for 1 month followed by methotrexate for 5 months (Profile AM). Number of flare-ups.	The number of flare-ups in patients treated with non-steroidal anti-inflammatory drugs for 1 month followed by methotrexate for 5 months (Profile AM) will be noted.	After 6 months of treatment
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by biotherapy (Profile AB). Number of species.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department. The number of species detected in the intestinal microbiota will be recorded.	24 hours after inclusion
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by biotherapy (Profile AB). Distribution of species.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department. The distribution of the various bacterial species in the microbiota will be recorded.	24 hours after inclusion
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by biotherapy (Profile AB). Diversity of species.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department. The diversity index according to the number of species and the number of functional groups will be recorded.	24 hours after inclusion
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by biotherapy (Profile AB). Number of species.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department. The number of species detected in the intestinal microbiota will be recorded.	After 1 month of treatment
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by biotherapy (Profile AB). Distribution of species.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department. The distribution of the various bacterial species detected in the intestinal microbiota will be recorded.	After 1 month of treatment
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by biotherapy (Profile AB). Diversity of species.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department. The diversity index according to the number of species and the number of functional groups will be recorded.	After 1 month of treatment
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by biotherapy (Profile AB). Number of species.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department. The number of species detected in the intestinal microbiota will be recorded.	After 6 months of treatment
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by biotherapy (Profile AB). Distribution of species.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department. The distribution of the various bacterial species detected in the intestinal microbiota will be recorded.	After 6 months of treatment
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by biotherapy (Profile AB). Diversity of species.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department. The diversity index according to the number of species and the number of functional groups will be recorded.	After 6 months of treatment
Response to treatment in patients treated with non-steroidal anti-inflammatory drugs followed by biotherapy (Profile AB)	The JADAS CRP clinical score will be used to rate the degree of activity of the disease. The Juvenile Arthritis Disease Activity Score (JADAS) is a recently developed composite tool for scoring disease activity in juvenile idiopathic arthritis. It is a composite disease activity score including four measures: the physician's global assessment of disease activity;; the parent/guardian's or patient's global assessment of overall wellbeing;; number of joints with active arthritis; and; C-reactive protein (CRP) which has been determined as an alternative inflammatory marker to the Erythrocyte Sedimentation Rate ESR. JADAS-CRP was calculated similarly to the original JADAS as the simple sum of its four components, yielding a global score of 0-40, 0-57 and 0-101 depending on the joint count used for the JADAS10-CRP, JADAS27-CRP and JADAS71-CRP, respectively.	After 6 months of treatment
Response to treatment in patients treated with non-steroidal anti-inflammatory drugs followed by biotherapy (Profile AB). Number of flare-ups.	The number of flare-ups in patients treated with non-steroidal anti-inflammatory drugs followed by biotherapy (Profile AB) will be noted.	After 6 months of treatment
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate then biotherapy (Profile AMB). Number of species.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department.The number of species detected in the intestinal microbiota will be recorded.	24 hours after inclusion
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate then biotherapy (Profile AMB). Distribution of species.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department.The distribution of the various bacterial species detected in the intestinal microbiota will be recorded.	24 hours after inclusion
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate then biotherapy (Profile AMB). Diversity of species.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department.The diversity index according to the number of species and the number of functional groups will be recorded.	24 hours after inclusion
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate then biotherapy (Profile AMB). Number of species.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department. The number of species detected in the intestinal microbiota will be recorded.	After 1 month of treatment
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate then biotherapy (Profile AMB). Distribution of species.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department. The distribution of the various bacterial species detected in the intestinal microbiota will be recorded.	After 1 month of treatment
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate then biotherapy (Profile AMB). Diversity of species.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department. The diversity index according to the number of species and the number of functional groups will be recorded.	After 1 month of treatment
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate then biotherapy (Profile AMB). Number of species.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department. The number of species detected in the intestinal microbiota will be recorded.	After 6 months of treatment
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate then biotherapy (Profile AMB). Distribution of species.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department. The distribution of the various bacterial species detected in the intestinal microbiota will be recorded.	After 6 months of treatment
Evolution of the intestinal microbiota in patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate then biotherapy (Profile AMB). Diversity of species.	Patients will provide 2 stool samples (one for analysis and one for the biobank) taken at the patient's home, preserved at -20°C and transported in a coolerbag to the hospital. One sample will be frozen to -80°C for the biobank and one sample will be kept at -20°C at the pediatric department. The diversity index according to the number of species and the number of functional groups will be recorded.	After 6 months of treatment
Response to treatment in patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate then biotherapy (Profile AMB)	The JADAS CRP clinical score will be used to rate the degree of activity of the disease. The Juvenile Arthritis Disease Activity Score (JADAS) is a recently developed composite tool for scoring disease activity in juvenile idiopathic arthritis. It is a composite disease activity score including four measures: the physician's global assessment of disease activity;; the parent/guardian's or patient's global assessment of overall wellbeing;; number of joints with active arthritis; and; C-reactive protein (CRP) which has been determined as an alternative inflammatory marker to the Erythrocyte Sedimentation Rate ESR. JADAS-CRP was calculated similarly to the original JADAS as the simple sum of its four components, yielding a global score of 0-40, 0-57 and 0-101 depending on the joint count used for the JADAS10-CRP, JADAS27-CRP and JADAS71-CRP, respectively.	After 6 months of treatment
Response to treatment in patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate then biotherapy (Profile AMB). Number of flare-ups.	The number of flare-ups in patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate then biotherapy (Profile AMB) will be noted.	After 6 months of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A:Correlation between intestinal microbiota of patients treated with non-steroidal anti-inflammatory drugs alone (Profile A) and the clinical stage of evolution of Juvenile Spondylarthitis.	The description of the intestinal microbiota profile according to INSERM laboratory Unit 1047 will be correlated with the clinical stage of the disease (on remission or acute flare) before and after treatment.	24 hours after inclusion
A:Correlation between intestinal microbiota of patients treated with non-steroidal anti-inflammatory drugs alone (Profile A) and the clinical stage of evolution of Juvenile Spondylarthitis.	The description of the intestinal microbiota profile according to INSERM laboratory Unit 1047 will be correlated with the clinical stage of the disease (on remission or acute flare) before and after treatment.	After 1 month of treatment
A:Correlation between intestinal microbiota of patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate (Profile AM) and the clinical stage of evolution of Juvenile Spondylarthitis.	The description of the intestinal microbiota profile according to INSERM laboratory Unit 1047 will be correlated with the clinical stage of the disease (on remission or acute flare) before and after treatment.	24 hours after inclusion
A:Correlation between intestinal microbiota of patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate (Profile AM) and the clinical stage of evolution of Juvenile Spondylarthitis.	The description of the intestinal microbiota profile according to INSERM laboratory Unit 1047 will be correlated with the clinical stage of the disease (on remission or acute flare) before and after treatment.	After 6 months of treatment
A:Correlation between intestinal microbiota of patients treated with non-steroidal anti-inflammatory drugs followed by biotherapy (Profile AB) and the clinical stage of evolution of Juvenile Spondylarthitis.	The description of the intestinal microbiota profile according to INSERM laboratory Unit 1047 will be correlated with the clinical stage of the disease (on remission or acute flare) before and after treatment.	24 hours after inclusion
A: Correlation between intestinal microbiota of patients treated with non-steroidal anti-inflammatory drugs followed by biotherapy (Profile AB) and the clinical stage of evolution of Juvenile Spondylarthitis.	The description of the intestinal microbiota profile according to INSERM laboratory Unit 1047 will be correlated with the clinical stage of the disease (on remission or acute flare) before and after treatment.	After 6 months of treatment
A:Correlation between intestinal microbiota of patients treated with non-steroidal anti-inflammatory drugs then methotrexate then biotherapy (Profile AMB) and the clinical stage of evolution of Juvenile Spondylarthitis.	The description of the intestinal microbiota profile according to INSERM laboratory Unit 1047 will be correlated with the clinical stage of the disease (on remission or acute flare) before and after treatment.	24 hours after inclusion
A:Correlation between intestinal microbiota of patients treated with non-steroidal anti-inflammatory drugs then methotrexate then biotherapy (Profile AMB) and the clinical stage of evolution of Juvenile Spondylarthitis.	The description of the intestinal microbiota profile according to INSERM laboratory Unit 1047 will be correlated with the clinical stage of the disease (on remission or acute flare) before and after treatment.	After 6 months of treatment
B:Correlation between bacterial translocation and response to treatment in patients treated with non-steroidal anti-inflammatory drugs alone (Profile A)	Pre- and post-therapeutic translocation and response to treatment (presence/absence: detection of DNA 16S in the blood, quantification by quantitative PCR and sequencing for identification).	24 hours after inclusion
B:Correlation between bacterial translocation and response to treatment in patients treated with non-steroidal anti-inflammatory drugs alone (Profile A)	Pre- and post-therapeutic translocation and response to treatment (presence/absence: detection of DNA 16S in the blood, quantification by quantitative PCR and sequencing for identification).	After 1 month of treatment
B:Correlation between bacterial translocation and response to treatment in patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate (Profile AM)	Pre- and post-therapeutic translocation and response to treatment (presence/absence: detection of DNA 16S in the blood, quantification by quantitative PCR and sequencing for identification).	24 hours after inclusion
B:Correlation between bacterial translocation and response to treatment in patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate (Profile AM)	Pre- and post-therapeutic translocation and response to treatment (presence/absence: detection of DNA 16S in the blood, quantification by quantitative PCR and sequencing for identification).	After 6 months of treatment
B:Correlation between bacterial translocation and response to treatment in patients treated with non-steroidal anti-inflammatory drugs followed by biotherapy (Profile AB)	Pre- and post-therapeutic translocation and response to treatment (presence/absence: detection of DNA 16S in the blood, quantification by quantitative PCR and sequencing for identification).	24 hours after inclusion
B:Correlation between bacterial translocation and response to treatment in patients treated with non-steroidal anti-inflammatory drugs followed by biotherapy (Profile AB)	Pre- and post-therapeutic translocation and response to treatment (presence/absence: detection of DNA 16S in the blood, quantification by quantitative PCR and sequencing for identification).	After 6 months of treatment
B:Correlation between bacterial translocation and response to treatment in patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate then biotherapy (Profile AMB)	Pre- and post-therapeutic translocation and response to treatment (presence/absence: detection of DNA 16S in the blood, quantification by quantitative PCR and sequencing for identification).	24 hours after inclusion
B:Correlation between bacterial translocation and response to treatment in patients treated with non-steroidal anti-inflammatory drugs followed by methotrexate then biotherapy (Profile AMB)	Pre- and post-therapeutic translocation and response to treatment (presence/absence: detection of DNA 16S in the blood, quantification by quantitative PCR and sequencing for identification).	After 6 months of treatment
C:Constitution of a biobank of samples from Profile A patients (treated with non-steroidal anti-inflammatory drugs alone)	All blood and stool samples used for the study will be deposited in the biobank for reference.	After 6 months of treatment
C: Constitution of a biobank for Profile AM patients (treated with non-steroidal anti-inflammatory drugs then methotrexate).	All blood and stool samples used for the study will be deposited in the biobank for reference.	After 6 months of treatment
C: Constitution of a biobank for Profile AB patients (treated with non-steroidal anti-inflammatory drugs then biotherapy)	All blood and stool samples used for the study will be deposited in the biobank for reference.	At the inclusion visit on Day 0
C: Constitution of a biobank for AMB patients (treated with non-steroidal anti-inflammatory drugs then methotrexate then biotherapy)	All blood and stool samples used for the study will be deposited in the biobank for reference.	At the inclusion visit on Day 0
Age of Profile A patients (treated with non-steroidal anti-inflammatory drugs alone)	Recorded in years	At the inclusion visit on Day 0
Weight of Profile A patients (treated with non-steroidal anti-inflammatory drugs alone)	Recorded in kilos	At the inclusion visit on Day 0
Height of Profile A patients (treated with non-steroidal anti-inflammatory drugs alone)	Recorded in cm.	At the inclusion visit on Day 0
Sex of Profile A patients (treated with non-steroidal anti-inflammatory drugs alone)	Male/Female	At the inclusion visit on Day 0
Previous treatment in Profile A patients (treated with non-steroidal anti-inflammatory drugs alone)	The investigators will record details of all treatment followed prior to diagnosis of juvenile spondylarthritis: NSAIDs : dosage and dates; Corticoids : dosage and dates; Antibiotics : dosage and dates; DMARDs : dosage and dates	At the inclusion visit on Day 0
Dietary habits in Profile A patients (treated with non-steroidal anti-inflammatory drugs alone)	The investigators will record details of patients' dietary habits and, more particularly, note all foods which are excluded.	At the inclusion visit on Day 0
Food allergies in Profile A patients (treated with non-steroidal anti-inflammatory drugs alone)	The investigators will record details of patients' food allergies.	At the inclusion visit on Day 0
Lifestyle of Profile A patients (treated with non-steroidal anti-inflammatory drugs alone)	The investigators will record details of the patient's lifestyle: Brothers and sisters (number and date of birth of each one); Communities (date of entry); Contact with animals	At the inclusion visit on Day 0
Age of Profile AM patients (treated with non-steroidal anti-inflammatory drugs then methotrexate)	Recorded in years	At the inclusion visit on Day 0
Weight of Profile AM patients (treated with non-steroidal anti-inflammatory drugs then methotrexate)	Recorded in kilos	At the inclusion visit on Day 0
Height of Profile AM patients (treated with non-steroidal anti-inflammatory drugs then methotrexate)	Recorded in cm.	At the inclusion visit on Day 0
Sex of Profile AM patients (treated with non-steroidal anti-inflammatory drugs then methotrexate)	Male/Female	At the inclusion visit on Day 0
Previous treatment in Profile AM patients (treated with non-steroidal anti-inflammatory drugs then methotrexate)	The investigators will record details of all treatment followed prior to diagnosis of juvenile spondylarthritis: NSAIDs : dosage and dates; Corticoids : dosage and dates; Antibiotics : dosage and dates; DMARDs : dosage and dates	At the inclusion visit on Day 0
Dietary habits in Profile AM patients (treated with non-steroidal anti-inflammatory drugs then methotrexate)	The investigators will record details of all patients' dietary habits and, more particularly, note all foods which are excluded.	At the inclusion visit on Day 0
Food allergies in Profile AM patients (treated with non-steroidal anti-inflammatory drugs then methotrexate)	The investigators will record details of all patients' food allergies.	At the inclusion visit on Day 0
Lifestyle in Profile AM patients (treated with non-steroidal anti-inflammatory drugs then methotrexate)	The investigators will record details of the patient's lifestyle: Brothers and sisters (number and date of birth of each one); Communities (date of entry); Contact with animals	At the inclusion visit on Day 0
Age of Profile AB patients (treated with non-steroidal anti-inflammatory drugs then biotherapy)	Recorded in years	At the inclusion visit on Day 0
Weight of Profile AB patients (treated with non-steroidal anti-inflammatory drugs then biotherapy)	Recorded in kilos	At the inclusion visit on Day 0
Height of Profile AB patients (treated with non-steroidal anti-inflammatory drugs for then biotherapy)	Recorded in cm.	At the inclusion visit on Day 0
Sex of Profile AB patients (treated with non-steroidal anti-inflammatory drugs then biotherapy)	Male/Female	At the inclusion visit on Day 0
Previous treatment in Profile AB patients (treated with non-steroidal anti-inflammatory drugs then biotherapy)	The investigators will record details of all treatment followed prior to diagnosis of juvenile spondylarthritis: NSAIDs : dosage and dates; Corticoids : dosage and dates; Antibiotics : dosage and dates; DMARDs : dosage and dates	At the inclusion visit on Day 0
Dietary habits in Profile AB patients (treated with non-steroidal anti-inflammatory drugs then biotherapy)	The investigators will record details of all patients' dietary habits and, more particularly, note all foods which are excluded.	At the inclusion visit on Day 0
Food allergies in Profile AB patients (treated with non-steroidal anti-inflammatory drugs then biotherapy)	The investigators will record details of all patients' food allergies.	At the inclusion visit on Day 0
Lifestyle in Profile AB patients (treated with non-steroidal anti-inflammatory drugs then biotherapy)	The investigators will record details of the patient's lifestyle: Brothers and sisters (number and date of birth of each one); Communities (date of entry); Contact with animals	At the inclusion visit on Day 0
Age of Profile AMB patients (treated with non-steroidal anti-inflammatory drugs then methotrexate biotherapy)	Recorded in years	At the inclusion visit on Day 0
Weight of Profile AMB patients (treated with non-steroidal anti-inflammatory drugs then methotrexate then biotherapy)	Recorded in kilos	At the inclusion visit on Day 0
Height of Profile AMB patients (treated with non-steroidal anti-inflammatory drugs then methotrexate then biotherapy)	Recorded in cm.	At the inclusion visit on Day 0
Sex of Profile AMB patients (treated with non-steroidal anti-inflammatory drugs then methotrexate then biotherapy)	Male/Female	At the inclusion visit on Day 0
Previous treatment in Profile AMB patients (treated with non-steroidal anti-inflammatory drugs then methotrexate then biotherapy)	The investigators will record details of all treatment followed prior to diagnosis of juvenile spondylarthritis: NSAIDs : dosage and dates; Corticoids : dosage and dates; Antibiotics : dosage and dates; DMARDs : dosage and dates	At the inclusion visit on Day 0
Dietary habits in Profile AMB patients (treated with non-steroidal anti-inflammatory drugs then methotrexate then biotherapy)	The investigators will record details of all patients' dietary habits and, more particularly, note all foods which are excluded.	At the inclusion visit on Day 0
Food allergies in Profile AMB patients (treated with non-steroidal anti-inflammatory drugs then methotrexate then biotherapy)	The investigators will record details of all patients' food allergies.	At the inclusion visit on Day 0
Lifestyle in Profile AMB patients (treated with non-steroidal anti-inflammatory drugs then methotrexate then biotherapy)	The investigators will record details of the patient's lifestyle: Brothers and sisters (number and date of birth of each one); Communities (date of entry); Contact with animals	At the inclusion visit on Day 0

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Collaborators: Assistance Publique Hopitaux De Marseille; University Hospital, Montpellier

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2021
• Primary Completion (Estimated): June 28, 2027
• Study Completion (Estimated): June 28, 2027

Study Registration Dates

• First Submitted: August 27, 2020
• First Submitted That Met QC Criteria: September 3, 2020
• First Posted (Actual): September 7, 2020

Study Record Updates

• Last Update Posted (Actual): December 20, 2023
• Last Update Submitted That Met QC Criteria: December 14, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Microbiota
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Spondylarthritis; Spondylitis; Spondylarthropathies
• Other Study ID Numbers: NIMAO/2019/TAT-01; 20.03.20.564 (Other Identifier: CNRIPH)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes